Widespread association of the Argonaute protein AGO2 with meiotic chromatin suggests a distinct nuclear function in mammalian male reproduction.

Autor:	Griffin KN; Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06510, USA., Walters BW; Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06510, USA., Li H; Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06510, USA., Wang H; Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA., Biancon G; Section of Hematology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510, USA.; Yale Comprehensive Cancer Center, Yale University School of Medicine, New Haven, Connecticut 06510, USA., Tebaldi T; Section of Hematology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510, USA.; Yale Comprehensive Cancer Center, Yale University School of Medicine, New Haven, Connecticut 06510, USA.; Department of Cellular, Computational and Integrative Biology (CIBIO), University of Trento, 38123 Trento, Italy., Kaya CB; Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06510, USA., Kanyo J; Keck MS & Proteomics Resource, Yale University School of Medicine, New Haven, Connecticut 06510, USA., Lam TT; Keck MS & Proteomics Resource, Yale University School of Medicine, New Haven, Connecticut 06510, USA.; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut 06520, USA., Cox AL; Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06510, USA., Halene S; Section of Hematology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06510, USA.; Yale Comprehensive Cancer Center, Yale University School of Medicine, New Haven, Connecticut 06510, USA.; Yale Stem Cell Center, Yale University School of Medicine, New Haven, Connecticut 06510, USA.; Yale Center for RNA Science and Medicine, Yale University School of Medicine, New Haven, Connecticut 06510, USA.; Department of Pathology, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06510, USA., Chung JJ; Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.; Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06510, USA., Lesch BJ; Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06510, USA.; Yale Comprehensive Cancer Center, Yale University School of Medicine, New Haven, Connecticut 06510, USA.; Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Jazyk:	angličtina
Zdroj:	Genome research [Genome Res] 2022 Sep 27; Vol. 32 (9), pp. 1655-1668. Date of Electronic Publication: 2022 Sep 27.
DOI:	10.1101/gr.276578.122
Abstrakt:	Argonaute 2 (AGO2) is a ubiquitously expressed protein critical for regulation of mRNA translation and vital to animal development. AGO2 protein is found in both cytoplasmic and nuclear compartments, and although its cytoplasmic role is well studied, the biological relevance of nuclear AGO2 is unclear. Here, we address this problem in vivo using spermatogenic cells as a model. We find that AGO2 transiently binds both chromatin and nucleus-specific mRNA transcripts of hundreds of genes required for sperm production during male meiosis in mice, and that germline conditional knockout (cKO) of Ago2 causes depletion of the encoded proteins. Correspondingly, Ago2 cKO males show abnormal sperm head morphology and reduced sperm count, along with reduced postnatal viability of offspring. Together, our data reveal an unexpected nuclear role for AGO2 in enhancing expression of developmentally important genes during mammalian male reproduction. (© 2022 Griffin et al.; Published by Cold Spring Harbor Laboratory Press.)
Databáze:	MEDLINE
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